The present invention is novel styryl pyrazoles and analogs thereof as well as pharmaceutical compositions and methods of use therefor.
Styryl isoxazole derivatives having cardiovascular activity are known. For example, European patent application Nos. 34754 and 5192 and German patent application No. 2943-405 having Derwent Abstract Nos. 66318 D/37, 84501 B/47 and 34567 D/20, respectively, disclose a compound of the general formula ##STR1## However, the present compounds differ from such references by a completely different side chain from that shown above linked to the phenyl at the 2-position through an ether group in each reference. Further, European patent application No. 5186 reviewed by Derwent Abstract No. 844908/47 discloses an intermediate isoxazole of the formula ##STR2## for which no pharmaceutical utility is disclosed.
Pyrazole derivatives having biological, specifically antiinflammatory, activity are found in Belgian Pat. Nos. 819,890 and 844,972 abstracted in Derwent Abstract Nos. 20948W/13 and 09405Y/06, respectively. A similar derivative is disclosed in German Pat. No. 2920941 of Derwent Abstract No. 86535C/49. However, each of these disclosed pyrazole derivatives requires substituents on adjacent carbons of the pyrazole ring.
Specifically excluded from the compounds of the present invention are the compounds of French Pat. No. 2104932 of Derwent Abstract No. 46150T-B useful as hypocholesterolemics, antiinflammatories, analgesics, sedatives, antipyretics, and in some instances diuretics. The compounds of the French Patent generally have the formula ##STR3##
Finally, of lesser interest numerous imidazoles are known having various pharmaceutical activity. For example, U.S. Pat. No. 3812111 and British Pat. No. 1,046,248 disclose compounds of general formula ##STR4## respectively wherein the - represents various substituents. However, the imidazoles are compounds differing from the present invention in that the compounds have a different ring system from the pyrazoles.
Thus, the novel compounds that are the present invention provide activity for use in the treatment of diseases in which 5-lipoxygenase enzyme activity contributes to the pathological condition. For example, the use for the present novel compounds, compositions and methods of use is for allergy, asthma, arthritis, skin disorders, such as psoriasis or acne, inflammation, for example, inflammatory bowel disease or pain, and further, also cardiovascular disorders including infarction, angina, arrhythmias, stroke, migraine, atherosclerosis, ulcers and other conditions particularly benefited by cytoprotective activity. An additional property of the present novel compounds now found to provide usefulness, for example, as sun screens, is absorption of ultraviolet light.